This is a continuous effort on a collaborative multi- phase project to investigate the immune response in both human and experimental animals after the infection with human hepatitis C virus. In the initial phase, the commercial testing kits were used to detect antibodies to HCV proteins in the known non-A, non-B hepatitis patient sera. This provided information on the serological data of hepatitis C virus infection and its relationship to other clinical determination. The second phase of the study concentrated on the identification of immune dominant epitopes and neutralizing epitopes. The scope of this phase of study was extensive and time consuming. The third phase of the project will encompass using the knowledge of immune response to develop preventative strategy and understanding the pathogenicity of this viral infection. Special attentions will be paid to identify the possible relationship between immune response and the high chronicity in HCV infected patients. During the last year, we initiated a new project to examine the potential of a HCV nucleic acid vaccine. The knowledge and information gained in this study were essential for building the foundation to investigate the development of a vaccine. The techniques and material developed in this study will also complement the need for each other. The long-term goal of both projects will lead to the development of models for the immune therapy of chronic vial infection of the liver.